作者：于春艳1，李丹丹1，周超1，辛瑞夏1，林晨晨2，王慧1，3，徐志伟1，张晓菊1

单位：

Units：

1.Department of Respiratory and Critical Care Medicine, Zhengzhou University People's Hospital/Henan Provincial People's Hospital, Zhengzhou 450000, China 2.Department of Respiratory and Critical Care Medicine, Henan University People's Hospital, Zhengzhou 450000, China 3.Xinxiang Medical University, Xinxiang 453000, China

关键词：

肺肿瘤；自身抗体；诊断

Keywords：

Lung neoplasms; Autoantibodies; Diagnosis

CLC：

R 734.2

DOI：

10.12114/j.issn.1008-5971.2021.00.141

Funds：

河南省医学科技攻关计划省部共建项目（SB201901091）

摘要：

背景　肺癌是发病率和死亡率较高的恶性肿瘤之一。大多数患者就诊时已处于中晚期阶段，5 年生 存率较低。由于低剂量CT（LDCT）及肿瘤标志物对早期肺癌的诊断效能不佳，因而寻找一种新的方法来诊断早期肺 癌成为一个热点问题。目的　探讨肿瘤相关自身抗体（T-AABs）对早期肺癌的诊断价值。方法　选取2019 年8 月— 2020 年11 月就诊于河南省人民医院并行LDCT 检查和7 种T-AABs〔p53、蛋白基因产物9.5（PGP9.5）、性别决定 基因家族2（SOX2）、G 抗原7（GAGE7）、RNA 解螺旋酶自身抗体4-5（GBU4-5）、黑色素瘤抗原A1（MAGE A1）、肿瘤相关基因（CAGE）〕检测的226 例肺结节患者为研究对象，根据疾病类型，将其分为早期肺癌组（146 例）和肺部良性病变组（80 例）。选取同期于河南省人民医院健康管理中心行LDCT 检查的无肺部异常的健康人37 例为健康对照组。检测研究对象7 种T-AABs，绘制受试者工作特征（ROC）曲线以分析各T-AABs 及其联合对早期 肺癌的诊断价值。分析早期肺癌组7 种T-AABs 阳性表达与CT 影像学特征之间的关联性。结果　早期肺癌组p53、 PGP9.5、SOX2、GAGE7、GBU4-5、MAGE A1、CAGE 高于健康对照组、肺部良性病变组（P ＜ 0.05）。ROC 曲线分 析结果显示，p53、PGP9.5、SOX2、GAGE7、GBU4-5、MAGE A1、CAGE 诊断早期肺癌的曲线下面积（AUC）分别为 0.60、0.59、0.63、0.64、0.69、0.64、0.59；7 种T-AABs 联合诊断早期肺癌的AUC 为0.74，灵敏度为33.56%，特异 度为92.31%，阳性预测值为84.48%。早期肺癌组7 种T-AABs 阳性97 例，阴性49 例。早期肺癌组7 种T-AABs 阳 性表达与边缘形态（毛刺征）、肿瘤边界（空泡征）、内部结构（胸膜凹陷征）有关联性（P ＜ 0.05）。结论　7种T-AABs （p53、PGP9.5、SOX2、GAGE7、GBU4-5、MAGE A1、CAGE）联合检测对早期肺癌有一定的诊断价值，早期肺癌患 者7 种T-AABs 阳性表达与部分CT 影像学特征有一定的关联性。

Abstract：

　Background　Lung cancer is one of the malignant tumors with high morbidity and mortality. Most of the patients are in the middle and late stage of tumor and the 5-year survival rate is low. Because of the poor diagnostic capabilities of low-dose computed tomography (LDCT) and tumor markers for the early stage of lung cancer, finding a new method to diagnose early stage of lung cancer has become a research hotspot. Objective　To explore the diagnostic value of tumor-associated autoantibodies (T-AABs) for early stage of lung cancer. Methods　Two hundred and twenty-six patients with pulmonary nodules which were confirmed by LDCT and had preformed T-AABs [p53, protein gene product 9.5 (PGP9.5) , SRY-box containing gene 2 (SOX2) , G antigen 7 (GAGE7) , RNA helicase autoantibodies 4-5 (GBU4-5) , melanoma antigen A1 (MAGE A1) , cancer associated gene (CAGE) ] test in Henan Provincial People's Hospital from August 2019 to November 2020 were selected as the research objects. According to the type of disease, they were divided into early stage of lung cancer group (146 cases) and benign lung disease group (80 cases) . And 37 healthy people who performed LDCT examination and had no lung abnormalities in the Health Management Center of Henan Provincial People's Hospital were selected as healthy control group during the same period. The seven T-AABs of the selected crowd were detected, and the receiver operator characteristic (ROC) curve was drawn to evaluate the diagnostic value of each T-AABs and their combination for early stage of lung cancer. The correlation between positive expression of seven T-AABs and CT imaging features of early stage of lung cancer was analyzed. Results　The p53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGE A1, CAGE in the early stage of lung cancer group were higher than those in the healthy control group and the benign lung disease group (P < 0.05) . The results of ROC curve analysis showed that the area under the curve (AUC) of p53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGE A1 and CAGE for the diagnosis of early stage of lung cancer were 0.60, 0.59, 0.63, 0.64, 0.69, 0.64 and 0.59, respectively; the AUC of seven T-AABs combination for the diagnosis of early stage of lung cancer was 0.74, with the sensitivity of 33.56%, and the specificity was 92.31%, and the positive predictive value was 84.48%. In the early lung cancer group, 97 cases of 7 T-AABs were positive and 49 cases were negative. The positive expression of seven T-AABs in the early stage of lung cancer group was correlated with edge shape (burr sign) , tumor border (vacuum sign) , and internal structure (pleural depression sign) (P < 0.05) . Conclusion　The combined detection of seven T-AABs (p53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGE A1, CAGE) has certain value in the diagnosis of early stage of lung cancer. The positive expression of seven T-AABs in patients with early stage of lung cancer is related to some CT imaging features.

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